Glaucoma is in ocular disorder associated with elevated intraocular pressures which are too high for normal fimction and may result in irreversible loss of visual function. If untreated, glaucoma may eventually lead to blindness. Ocular hypertension, i.e., the condition of elevated intraocular pressure without optic nerve head damage or characteristic glaucomatous visual field defects, is now believed by many ophthalmologists to represent the earliest phase of glaucoma.
Compounds of structural Formula: ##STR1## the individual diastereomers, the individual enantiomers or mixtures thereof, or an ophthalmologically acceptable salt thereof, wherein:
A is carbon or nitrogen; PA1 Z is NHR or --OR; PA1 R is C.sub.1-6 alkyl, either straight or branched chain; PA1 R.sup.1 is PA1 X is --SO2-- or --C(O)--; PA1 b) C.sub.3-5 alkenyl, especially allyl; PA1 c) C.sub.3-5 alkynyl, especially propargyl; PA1 d) hydrogen; or PA1 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl, PA1 A is carbon or nitrogen; PA1 Z is NHR or --OR; PA1 R is C.sub.1-6 alkyl, either straight or branched chain; PA1 R.sup.1 is PA1 X is --SO.sub.2 -- or --C(O)--; PA1 b) C.sub.3-5 alkenyl, especially allyl; PA1 c) C.sub.3-5 alkynyl, especially propargyl; PA1 d) hydrogen; or PA1 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl PA1 b) C.sub.3-5 alkenyl, especially allyl; PA1 c) C.sub.3-5 alkynyl, especially propargyl; PA1 d) hydrogen; or PA1 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl, PA1 A is carbon or nitrogen; PA1 Z is NHR or --OR; PA1 R is C.sub.1-6 alkyl, either straight or branched chain; PA1 R.sup.1 is PA1 X is --SO.sub.2 -- or --C(O)--; PA1 b) C.sub.3-5 alkenyl, especially allyl; PA1 c) C.sub.3-5 alkynyl, especially propargyl; PA1 d) hydrogen; or PA1 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl
a) C.sub.1-5 alkyl, either straight or branched chain, especially n-propyl or isobutyl; PA2 b) C.sub.3-5 alkenyl, especially allyl; PA2 c) C.sub.3-5 alkynyl, especially propargyl; PA2 d) hydrogen; or PA2 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl; and PA2 a) C.sub.1-5 alkyl, either straight or branched chain, especially n-propyl or isobutyl; PA2 b) C.sub.3-5 alkenyl, especially allyl; PA2 c) C.sub.3-5 alkynyl, especially propargyl; PA2 d) hydrogen; or PA2 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl; and PA2 a) C.sub.1-5 alkyl, either straight or branched chain, especially n-propyl or isobutyl; PA2 b) C.sub.3-5 alkenyl, especially allyl; PA2 c) C.sub.3-5 alkynyl, especially propargyl; PA2 d) hydrogen; or PA2 e) C.sub.1-4 alkoxy-C.sub.1-4 alkyl; and
are known from U.S. Pat. Nos. 4,797,413 and 5,157,129. The compounds are known to be topically effective carbonic anhydrase inhibitors (TCAI's) useful in the treatment of ocular hypertension. The synthesis of the compounds involves the reduction of a sulfo-ketone to a trans-hydroxy sulfone precursor to the above-noted compounds. However, the synthetic processes described for their preparation result in diastereomeric or racemic products which must be separated and resolved, with concomitant loss of at least 50% of the product, to obtain the most active enantiomer.
Now with the present invention there is provided a novel microbial process for the bioconversion of the sulfo-ketone intermediate to a trans-hydroxy sulfone intermediate.